Vomocytosis: Too Much Booze, Base, or Calcium?

Melissa Cruz-Acuña,Noah Pacifici,Jamal S Lewis,Danielle A Garsin

doi:10.1128/mbio.02526-19

Abstract

Macrophages are well known for their phagocytic activity and their role in innate immune responses. Macrophages eat non-self particles, via a variety of mechanisms, and typically break down internalized cargo into small macromolecules. However, some pathogenic agents have the ability to evade this endosomal degradation through a nonlytic exocytosis process termed vomocytosis. This phenomenon has been most often studied for Cryptococcus neoformans, a yeast that causes roughly 180,000 deaths per year, primarily in immunocompromised (e.g., human immunodeficiency virus [HIV]) patients. Existing dogma purports that vomocytosis involves distinctive cellular pathways and intracellular physicochemical cues in the host cell during phagosomal maturation. Moreover, it has been observed that the immunological state of the individual and macrophage phenotype affect vomocytosis outcomes. Here we compile the current knowledge on the factors (with respect to the phagocytic cell) that promote vomocytosis of C. neoformans from macrophages.

Highlights

WHAT GOES IN MUST COME OUT?Phagocytosis by innate immune cells is important for cell-to-cell communication, metabolism, homeostasis, and organism survival [1,2,3,4]
Using a zebrafish model of cryptococcal disease, this study showed that reducing extracellular-signal-regulated kinase 5 (ERK5) activity in vivo stimulates vomocytosis and results in reduced dissemination of infection, likely due to expulsion before macrophage migration
While this report showed the importance of cathepsin B in the activation of host protection against C. neoformans in vivo, Smith et al showed that macrophage infection with C. neoformans results in lack of cathepsin L activation, which is a phagosome maturation late-stage marker

Summary

Introduction

WHAT GOES IN MUST COME OUT?Phagocytosis by innate immune cells is important for cell-to-cell communication, metabolism, homeostasis, and organism survival [1,2,3,4]. Vomocytosis (often referred to as nonlytic exocytosis) has been observed in C. neoformans-infected macrophages. Studies suggest that C. neoformans mechanically disrupts host cells through proliferation within the phagosome and possibly via production of large amounts of polysaccharide capsule [38, 39].

Results

Conclusion